In recent years, the stent treatment has become popular in the field of medical treatment, in which an affected area of the coronary artery having been constricted as a result of progress of arteriosclerosis is mechanically expanded with the aid of a balloon catheter, followed by placement of a metallic stent within the vascular lumen to restore the flow of blood. Development of the stent treatment is indeed a good news to patients suffering from arterial stenosis. However, placement of such a stent in the coronary artery, of which constriction or occlusion is highly fatal, has been found that involving the probability of postoperative treatment required reaches 20 to 30% because even though the stent has been placed, vascular intimal hyperplasia occurs with the vascular lumen narrowed consequently. In view of the above, in order to decrease the in-stent restenosis, attempts have been made to design a stent of a type having a surface carrying a drug effectively to exhibit restenosis prevention effects so that the drug, when the stent is placed in an artery, can be eluted in a controlled manner within the vascular lumen to thereby suppress the restenosis. Those attempts have led to commercialization of drug-eluting stents (hereinafter referred to as DES) utilizing sirolimus (immunosuppressor) and paclitaxel (anticancer drug). However, since those drugs have an effect of inhibiting the proliferation of vascular cells (endothelial cells and smooth muscle cells) by acting on the cell cycle thereof, not only can the vascular intimal hyperplasia resulting from an excessive proliferation of the smooth muscle cells be suppressed, but proliferation of endothelial cells once denuded during placement of the stent is also suppressed, resulting in adverse effect that the repair or treatment of the intima of a blood vessel becomes retarded. In view of the fact that thrombosis tends to occur easily at the site being not covered with endothelial cells in the intima of a blood vessel, an antithrombotic drug must be administrated for a prolonged time, say, half a year or so and, even though the antithrombotic drug is administrated, there is a risk that the late thrombosis may lead to sudden death.
The first event occurring in the causal sequence from the intravascular stent placement to the in-stent restenosis is said to be an “injury to the blood vessel at the time of placement of the stent, particularly an injury to the endothelial cells”, which leads to a causal consequence of “formation of blood clots”, “adhesion or infiltration of leukocytes into the blood vessel wall”, “inflammation”, “proliferation of smooth muscle cells” and “stenosis” in this order. Accordingly, it is expected that suppression of the formation of blood clots is effective to inhibit the stenosis and, based on this view, application of an antithrombotic drug such as, for example, heparin or hirudin to form a drug-eluting stent has been strenuously tried at the initial stage of development thereof, but the clinical effectiveness thereof has not been ascertained. Now that the drug-eluting stent utilizing sirolimus or paclitaxel has been widespread in these days, the drug-eluting stent coated with the antithrombotic drug has been a minor candidate in the development of drug-eluting stents. At present, however, the practicality of the drug-eluting stent carrying a vascular intimal hyperplasia inhibitor, which does not inhibit proliferation of endothelial cells, has not yet been proved.
On the other hand, the Patent Document 1 listed below discloses in an embodiment of the invention thereof, a stent capable of eluting both of argatroban (anticoagulant agent) and cilostazol (antiplatelet agent). The Patent Document 2 also listed below discloses the elution rate of the drug from a polymer film containing argatroban, immersed in a solution of phosphate buffer (pH 7.4) for three weeks. In any event, however, surprising effect of inhibiting the vascular intimal hyperplasia while the drug is carried by the stent has not yet been observed.